Scientists have bred a genetic ‘supermouse’ that is apparently
‘invulnerable’ to cancer, reported BBC news today. The mice were implanted with a particular gene (Par-4) which...

Scientists have bred a genetic ‘supermouse’ that is apparently ‘invulnerable’ to cancer, reported BBC News today. The mice were implanted with a particular gene (Par-4) which selectively attacks cancer cells whilst leaving healthy cells intact. They say that the mice are subsequently resistant to all forms of cancer, and therefore if this gene could be implanted into humans it could be a breakthrough cancer treatment.

The news stories are based on research that involved inserting a particular region of DNA from the par-4 gene into mice and looking at the effects that this had on the animal’s growth and life-span, and on the growth of spontaneous or induced cancerous tumours.

This research does appear to demonstrate that the genetically modified mice had a resistance to cancer and suffered no detrimental effects. This development is likely to lead to further research, but whether Par-4 will have a role in the prevention or treatment of any type of cancer in humans will not become clear for many years.

Where did the story come from?

Yanming Zhao and colleagues of University of Kentucky and University of Nebraska, USA, carried out the research, which was funded by the National Cancer Institute. The study was published in the peer-reviewed medical journal: Cancer Research.

What kind of scientific study was this?

This was an experimental animal study investigating a particular protein, prostate apoptosis response-4 (Par-4), which has previously been found to act as a tumour-suppressor. The protein, produced by the gene par-4, was first identified by researchers looking at prostate cancer cells, who found that it appeared to have a role in inducing the body’s ability to search out and destroy damaged and faulty cells. Previous research has found that mice that have had the par-4 gene removed develop various spontaneous tumours.

The cancer fighting properties of Par-4 depend on one region of amino acids (the building blocks of proteins) called the SAC region. The researchers looked at whether sustained production of this amino acid sequence, promoted by the turned on par-4 gene, would be tolerated by normal healthy mice cells, and whether it would suppress tumours.

The researchers genetically engineered mice by inserting the DNA that codes for the SAC region into fertilised mouse embryos. They attached the DNA encoding the SAC region to another piece of DNA that would ensure that the protein would be expressed (turned on) in all the mice tissues.

The mice growth and their ability to reproduce was then observed and recorded, and they were monitored to see whether they developed cancers. The researchers also looked at how the mice cells responded to exposure to cancer inducing genes.

The mice were also bred with another strain of genetically engineered mice that were susceptible to mouse prostate cancer. They followed the offspring until they were 28 months of age. Any prostate tumours that developed were extracted, weighed and analysed.

What were the results of the study?

The researchers found that the mice genetically engineered to express the SAC region of the Par-4 protein in all their tissues had normal growth and development and were fertile. They could also pass on the SAC transgene to their offspring.

When infected with viruses carrying carcinogenic genes, the cells from the skin of embryonic mice with the SAC transgene were less likely be transformed into cancerous cells than cells from unmodified, control mice. This appeared to be because the presence of the SAC protein promotes cell death when exposed to cancer-causing genes.

The strain of mice used in the experiments were reported to have a high incidence of developing spontaneous liver cancers and lymphomas. The researchers therefore monitored the livers and spleens of the mice and found that none of the assessed SAC transgene mice developed these cancers, while about 50% of the mice who did not carry the SAC transgene did.

The researchers then compared mice carrying both the SAC transgene and a transgene making them susceptible to prostate cancer, with mice carrying the prostate cancer susceptibility gene alone. They found that at six months, all the mice not carrying the SAC transgene developed prostate cancer, compared to about 21% of the mice who did. Again, they found that the SAC gene was causing the cancerous cells to undergo cell death, and that the cells that successfully formed tumours had stopped expressing the SAC transgene.

What interpretations did the researchers draw from these results?

The authors conclude that the SAC domain of the par-4 gene is well tolerated by mice and has no effect on growth or fertility. It also appears to give protection against induced cancerous change and to give increased resistance in particular to prostate tumour growth.

They say that it ‘provides an ideal molecule for the therapy of cancer’ by causing suppression of tumours but without compromising normal tissue function or life span.

What does the NHS Knowledge Service make of this study?

This research demonstrates that genetically engineered mice who express the SAC region of the par-4 gene appeared to have a normal lifespan and showed resistance to laboratory-induced cancerous growths.

However, as with all animal studies, direct translation to humans is not possible. The technique involved the insertion of a section of DNA into a mouse embryo. This type of technique is unlikely to be used in humans. There are ethical doubts on making irreversible changes to human DNA and concern that random insertion of the transgene into the host’s DNA may cause harmful mutations.

This research considerably advances our knowledge, however it will be many years before we are at a stage where this could possibly be applied to preventing or treating cancer in humans.

Sir Muir Gray adds...

Genetic factors do influence cancer growth, so genetic modification will have a part to play in controlling disease.